2024-09-12 14:57:04
In 1817, James Parkinson, a British physician, published « An Essay on the Shaking Palsy » (“An Essay on the Agitating Paralysis”), in which he first described cases of patients with the neurodegenerative disorder that now bears his name, Parkinson’s disease.
The characteristic tremors of patients with Parkinson’s disease result from the death of brain cells that control movement. To date, there is no treatment capable of stopping or slowing down this process, which affects more than 10 million people worldwide, including approximately one million Americans, making Parkinson’s disease the second most common neurodegenerative disease in the United States (in France, where there are more than 167,000 sick peoplethis condition also ranks second among the most common neurodegenerative diseases, editor’s note).
Within our laboratory, we work on the Parkinson’s diseaseFor more than a decade, we have focused our efforts in particular on elucidating the role played by mitochondria – the microscopic powerhouses that fuel our cells – in disease.
In doing so, we have identified a protein which could open new therapeutic avenues, not only to treat Parkinson’s disease, but also other brain disorders.
Mitochondrial dynamics and neurodegeneration
Table of Contents
Table of Contents
Unlike true power plants, which do not vary in size or location, mitochondria are dynamic: their number is constantly changing, as are their size and location; to meet the needs of the cell in which they are located, they move between its different compartments. These mitochondrial dynamics are essential not only for the proper functioning of mitochondria, but also for the overall health of cells.
To understand why, we need to think of the cell as a factory: to ensure optimal and smooth functioning, several departments must work together. Given that many major cellular processes are interconnected, the alteration of mitochondrial dynamics that disrupts one department could, through a kind of domino effect, affect other departments, with the risk that one collective dysfunction causes cell death.
Mitochondria produce the energy that powers cells. OpenStax
Various relatively recent studies have revealed the existence of a link between imbalances in mitochondrial processes and different neurodegenerative diseaseswhose Parkinson’s disease. In many neurodegenerative disorders, certain disease-related factors, such as toxic proteins and environmental neurotoxins, disrupt the harmony between mitochondrial fusion and division.
Altered mitochondrial dynamics also compromise the waste cleaning and recycling process inside the cell, resulting in an accumulation of toxic proteins that leads to the formation of harmful aggregates. In Parkinson’s disease, the presence of these aggregates is a disease marker.
For all these reasons, our team hypothesized that restoring mitochondrial function by manipulating its own dynamics could protect against neuronal dysfunction and cell death.
Targeting mitochondria to treat Parkinson’s disease
In our efforts to restore mitochondrial function in Parkinson’s disease, we targeted a key protein, Drp1 (for dynamin-related protein 1or “dynamin-related protein 1” in English), which controls mitochondrial dynamics. Naturally abundant in cells, this protein moves towards the mitochondria when they divide (in this way, the mitochondria become smaller, and acquire greater mobility as well as better “quality control” of their functions). However, excessive activity of Drp1 causes excessive divisions, leading to fragmentation of the mitochondria and their dysfunction.
Using different laboratory models of Parkinson’s disease, including crops of neuronal cells as well as various lines of rats and of mousewe found that the presence of environmental toxins and toxic proteins linked to Parkinson’s disease causes mitochondria to fragment. The presence of these fragmented mitochondria also coincided with an accumulation of said toxic proteins inside neuronal cells, degrading their condition until they eventually die. In parallel, we also observed behavioral changes in the rats: their movements were altered.
However, by reducing the activity of Drp1, we were able to restore mitochondrial activity. This intervention protected the neurons from the disease, allowing them to continue functioning. Furthermore, during this work, the results of which were published in 2024, we identified a additional benefit to targeting Drp1.
Restoring mitochondrial function could represent a new approach to treating neurodegenerative diseases.
Highwaystarz-Photography/iStock via Getty Images Plus
In our experiments, we exposed neuronal cells to manganese, a heavy metal which is known to increase the risk of Parkinson’s disease and is involved in neurodegenerative processes. To our surprise, we found that this element was more harmful to the cell’s waste recycling system than for its mitochondria.
Concretely, exposure to manganese results in an accumulation of toxic proteins that occurs before the mitochondria themselves become dysfunctional. However, in this context, inhibition of Drp1 reactivated the waste recycling system, eliminating toxic proteins despite the presence of manganese.
Taken together, our results indicate that it may be possible to protect nerve cells from degeneration by inhibiting Drp1 in various ways. We have already identified some compounds – approved by the FDA (Food and Drug Administration, the American administration responsible for monitoring food and drug products, editor’s note) – capable of targeting this protein. We are now testing them to assess their potential as treatments for Parkinson’s disease.
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– How do mitochondrial dynamics influence the progression of Parkinson’s disease?
Unlocking the Secrets of Parkinson’s Disease: The Role of Mitochondrial Dynamics
Parkinson’s disease, a neurodegenerative disorder affecting over 10 million people worldwide, is a pressing health concern that has puzzled medical professionals for centuries. The disease was first described by British physician James Parkinson in 181
How do mitochondrial dynamics contribute to the symptoms of Parkinson’s disease?
Unlocking the Secrets of Parkinson’s Disease: The Role of Mitochondrial Dynamics
Parkinson’s disease, a debilitating neurodegenerative disorder, has been shrouded in mystery for centuries. However, since James Parkinson’s pioneering work in 1817, significant progress has been made in understanding the disease’s underlying mechanisms. Over 200 years later, researchers continue to uncover new insights into the intricate relationship between mitochondria and neurodegeneration. In this article, we’ll delve into the fascinating world of mitochondrial dynamics and its potential to revolutionize Parkinson’s disease treatment.
The Silent Suffering of Parkinson’s Patients
Parkinson’s disease affects over 10 million people worldwide, making it the second most common neurodegenerative disease in the United States and France. The characteristic tremors of Parkinson’s patients result from the death of brain cells that control movement. Despite significant advancements in medical research, there is currently no treatment capable of stopping or slowing down this process.
Unraveling the Mystery of Mitochondrial Dynamics
Mitochondria, the microscopic powerhouses that fuel our cells, play a pivotal role in maintaining cellular health. Unlike traditional power plants, mitochondria are dynamic, constantly changing in size, location, and function to meet the cell’s energy demands. This complex interplay, known as mitochondrial dynamics, is essential for proper cellular functioning.
In a healthy cell, mitochondrial dynamics ensure the proper distribution of energy resources. However, when this delicate balance is disrupted, it can have far-reaching consequences, leading to cellular dysfunction and even death. Recent studies have revealed a compelling link between imbalances in mitochondrial processes and various neurodegenerative diseases, including Parkinson’s disease.
Targeting Mitochondria to Treat Parkinson’s Disease
Researchers have identified a protein that could open new therapeutic avenues for treating not only Parkinson’s disease but also other brain disorders. By targeting mitochondria, scientists may be able to develop novel treatments that address the root causes of neurodegeneration.
How Do Mitochondrial Dynamics Influence the Progression of Parkinson’s Disease?
Mitochondrial dynamics play a crucial role in the progression of Parkinson’s disease. When mitochondrial processes are disrupted, it can lead to a cascade of cellular dysfunctions, ultimately resulting in cell death. Understanding the complex interplay between mitochondrial dynamics and neurodegeneration is essential for the development of effective treatments.
The Future of Parkinson’s Disease Treatment
The discovery of the protein’s role in mitochondrial dynamics has the potential to revolutionize Parkinson’s disease treatment. By targeting mitochondria, researchers may be able to develop novel therapies that slow or even stop the progression of the disease.
the intricate relationship between mitochondrial dynamics and neurodegeneration holds the key to unlocking the secrets of Parkinson’s disease. As researchers continue to unravel the mysteries of this complex disorder, they may uncover new therapeutic avenues that bring hope to millions of patients worldwide.
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Optimized Article Structure:
Introduction: Brief overview of Parkinson’s disease and its history
The Silent Suffering of Parkinson’s Patients: Statistics and facts about the disease
Unraveling the Mystery of Mitochondrial Dynamics: Explanation of mitochondrial dynamics and their importance
Targeting Mitochondria to Treat Parkinson’s Disease: Discussion of new therapeutic avenues
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